The present invention generally relates to the delivery of medicaments and other agents. More specifically, the present invention relates to the delivery of medicaments and agents using chewing gum formulations.
It is of course known to provide agents to individuals for various purposes. These agents can be used to treat diseases and as such are typically referred to as drugs or medicaments. Likewise, the drugs or medicaments can be used for prophylactic purposes. Still, it is known to provide agents to an individual for a variety of non-medical purposes including enhancing performance or maintaining or initiating alertness. There are a great variety of such agents. These agents run the gamut from stimulants such as caffeine to drugs such as analgesics, tranquilizers, cardiovascular products, insulin, etc. Some such agents are taken on an as needed basis while other agents must be taken at regular intervals by the individual.
Typically, drugs (medicaments) are administered parenterally or enterally. Of course, parenteral administration is the administration of the drug intravenously directly into the blood stream. Enteral refers to the administration of the drug into the gastrointestinal tract. In either case, the goal of the drug administration is to move the drug from the site of administration towards the systemic circulation.
Except when given intravenously, a drug must traverse several semipermeable cell membranes before reaching general circulation. These membranes act as a biological barrier that inhibits the passage of drug molecules. There are believed to be four processes by which drugs move across a biological barrier: passive diffusion; facilitated diffusion; active transport; and pinocytosis.
Passive diffusion is the transport across the cell membrane wherein the driving force for the movement is the concentration gradient of the solute. In orally administered drugs, this absorption occurs in the small intestines. Facilitated diffusion is believed to be based on a carrier component that combines reversibly with the substrate molecule at the cell membrane exterior. The carrier substrate complex diffuses rapidly across the membrane with release of the substrate at the interior surface. Active transport requires an energy expenditure by the cell and appears to be limited to agents with structural similarities to normal body constituents. These agents are usually absorbed from specific sites in the small intestines. Pinocytosis refers to the engulfing of particulars or fluid by a cell. It is believed to play a minor role in drug transport. Merck Manual, 16th Edition, pp. 2598-2599.
In determining the efficacy of a drug and the effectiveness of the use of a drug to treat a disease, drug absorption is a critical concern. Drug absorption refers to the process of drug movement from the site of administration toward the systemic circulation.
Oral administration of drugs is by far the most common method. When administered orally, drug absorption usually occurs due to the transport of cells across the membranes of the epithelial cells within the gastrointestinal tract. Absorption after oral administration is confounded by numerous factors. These factors include differences down the alimentary cannel in: the luminal pH; surface area per luminal volume; perfusion of tissue, bile, and mucus flow; and the epithelial membranes. See Merck Manual at page 2599.
A further issue effecting the absorption of orally administered drugs is the form of the drug. Most orally administered drugs are in the form of tablets or capsules. This is primarily for convenience, economy, stability, and patient acceptance. Accordingly, these capsules or tablets must be disintegrated or dissolved before absorption can occur. There are a variety of factors capable of varying or retarding disintegration of solid dosage forms. Further, there are a variety of factors that effect the dissolution rate and therefore determine the availability of the drug for absorption. See Merck Manual at page 2600.
Parental administration allows for the direct placement of the drug into the blood stream. This usually insures complete delivery of the dose to the general circulation. However, administration by a route that requires drug transfer through one or more biologic membranes to reach the blood stream precludes a guarantee that all of the drug will eventually be absorbed. Even with parental administration, because capillaries tend to be highly porous, the perfusion (blood flow/gram of tissue) is a major factor in the rate of absorption. Thus, the injection site can markedly influence a drugs"" absorption rate; e.g., the absorption rate of diazepam injected IM into a site with poor blood flow can be much slower than following an oral dose. See Merck Manual at page 2601.
Not only is drug absorption an issue in drug delivery but also the bioavailability of the drug is also critical. Bioavailability is defined as the rate at which and the extent to which the active moiety (drug or metabolite) enters the general circulation, thereby gaining access to the site of action. Bioavailability depends upon a number of factors, including how a drug product is designed and manufactured, its physicochemical properties, and factors that relate to the physiology and pathology of the patient. See Merck Manual at page 2602.
When a drug rapidly dissolves from a drug product and readily passes across membranes, absorption from most site administration tends to be complete. This is not always the case for drugs given orally. Before reaching the vena cava, the drug must move down the alimentary cannel and pass through the gut wall and liver, which are common sites of drug metabolism. Thus, the drug may be metabolized before it can be measured in the general circulation. This cause of a decrease in drug input is called the first pass effect. A large number of drugs show low bioavailability owing to an extensive first pass metabolism. The two other most frequent causes of low bioavailability are insufficient time in the GI tract and the presence of competing reactions. See Merck Manual at page 2602.
Bioavailability considerations are most often encountered for orally administered drugs. Differences in bioavailability can have profound clinical significance.
Although parental administration does provide a method for eliminating a number of the variables that are present with oral administration, parental administration is not a preferable route. Typically, parental administration requires the use of medical personnel and is just not warranted nor practical for the administration of most agents and drugs, e.g., analgesics. Even when required parenteral administration is not preferred due to patient concerns including comfort, infection, etc., as well as the equipment and costs involved. However, despite best efforts certain therapies require parenterally injected drugs. For example, research for decades has focused on an attempt to deliver insulin to an individual through a non-parental means. Despite such efforts today insulin is still only administered intravenously.
There is therefore a need for an improved method of delivering drugs and agents to an individual.
The present invention provides improved methods for delivering a medicament or agent to an individual. To this end, chewing gum, specifically a coated chewing gum product, is provided including a medicament or agent. The medicament or agent is present within the coating or shell that substantially encloses a gum center (the water soluble portion and insoluble base portion). It has been found that by chewing the overcoated chewing gum, or in certain situations even placing the coated chewing gum in the mouth, the medicament or agent is released from the chewing gum. Continuing to chew the chewing gum, it is believed, creates a pressure within the buccal cavity forcing the agent or medicament directly into the systemic system of the individual through the oral mucosa contained in the buccal cavity. This greatly enhances the absorption of the drug into the systemic system as well as the bioavailability of the drug within the system.
Improved formulations including medicaments or agents are also provided by the present invention.
To this end, the present invention provides a coated chewing gum composition including a gum center. The gum center includes a water soluble portion and a water insoluble portion. A coating substantially surrounds the gum center, the coating comprises at least 50% by weight of the chewing gum product. The product includes a medicament or agent.
In an embodiment, the coating includes a sufficient amount of a masking agent to improve the organoleptic properties of the coating containing the medicament. The masking agent may be chosen from the group consisting of: sucralose; zinc gluconate; ethyl maltol; glycine; acesulfame-K; aspartame; saccharin; fructose; xylitol; spray dried licorice root; glycerrhizine; dextrose; sodium gluconate; glucono delta-lactone; ethyl vanillin; vanillin; normal and high-potency sweeteners; and a variety of appropriate flavors.
In an embodiment, the coating includes a high-intensity sweetener. In a further embodiment, the high-intensity sweetener is chosen from the group consisting of aspartame, sucralose, and acesulfame-K.
In an embodiment, the gum center comprises approximately 30% to about 90% by weight water insoluble gum base.
In an embodiment, the formulation creates a saliva content of medicament of at least 5 ppm to about 66% medicament by weight in the saliva, depending on the medicament.
In an embodiment, the coating comprises up to 75% by weight of the chewing gum composition.
In an embodiment, the coating is a recrystallized granular coating.
In an embodiment, the coating is an amorphous coating.
In an embodiment, the coating is a powder coating.
In an embodiment, the chewing gum is chewed for at least 2 minutes.
In an embodiment, the medicament is chosen from the group consisting of: analgesics; muscle relaxants; antacids; antihistamines; decongestants; anti-inflammatories; antibiotics; antivirals; psychotherapeutic agents; insulin; and cardiovascular agents.
In an embodiment, the chewing gum including the medicament is chewed at least twice a day.
In an embodiment, two pieces of chewing gum are chewed at a time.
In another embodiment of the present invention a method of drug delivery is provided. The method comprising the steps of: providing a chewing gum that includes a coating that comprises at least 50% by weight of the chewing gum, the coating including a medicament that substantially surrounds a gum center; chewing the chewing gum to cause the medicament to be released from the chewing gum composition into the buccal cavity of the chewer; and continuing to chew the chewing gum thereby creating a fluid pressure causing the medicament to enter the systemic system of the chewer through the oral mucosa contained in the buccal cavity.
In a further embodiment of the present invention, a method for reducing the amount of agent necessary to achieve an effect in an individual as compared to a typical agent that is swallowed is provided. The method comprises the steps of: providing a chewing gum including a coating that surrounds a gum center, the coating comprising at least 50% by weight of the total chewing gum, the coating including an agent that is typically swallowed by an individual to achieve a specific effect. However, the coating includes less than the typical amount of agent that is swallowed by the individual to achieve the effect; chewing the chewing gum and thereby causing the agent to be released into the salvia of the individual; and continuing to chew the chewing gum forcing the agent through the mucous membranes in a buccal cavity of the individual.
In an embodiment of the method, the agent is a medicament. In an embodiment of the method, the medicament is chosen from the group consisting of: analgesics; muscle relaxants; antihistamines; decongestants; antacids; anti-inflammatories; antibiotics; antivirals; psychotherapeutic agents; and cardiovascular agents.
In an embodiment of the method, the chewing gum is chewed for at least 2 minutes.
In an embodiment of the method, the chewing gum creates a saliva content of agent of at least 0.5 to about 5000 ppm depending on the medicament.
In an embodiment of the method, the agent is a stimulant.
In a still further embodiment of the present invention, a method of enhancing an individual""s performance is provided. The method comprising the steps of: providing chewing gum including a performance enhancing amount of caffeine in a coating that surrounds a chewing gum center, the coating comprising at least 50% by weight of the chewing gum; and chewing the chewing gum not more than ten minutes before the performance.
In an embodiment, the performance to be enhanced is athletic.
In an embodiment, the performance to be enhanced is cognitive.
In an embodiment, the performance to be enhanced is alertness.
In an embodiment, the chewing gum is chewed not more than 5 minutes before the performance.
In yet another embodiment of the present invention a method of delivering a medicament is provided. The method comprising the steps of: providing a chewing gum including a coating that comprises at least 50% by weight of the chewing gum and surrounds a gum center and includes a medicament; and chewing the chewing gum for at least 2 minutes.
Yet further, in an embodiment of the present invention a method of increasing the stimulatory effect of a stimulant that has been previously ingested by an individual is provided. The method comprising the steps of: providing a chewing gum that includes a coating that contains a stimulant and surrounds a gum center the coating comprising at least 50% by weight of the chewing gum; and chewing the chewing gum causing the stimulant to be released by the chewing gum and forced into the oral mucosa of the individual.
In a still further embodiment of the present invention a chewing gum composition is provided. The chewing gum includes a gum center including a water soluble portion and a water insoluble portion, the water insoluble portion comprising at least 30% by weight of the gum center. The coating surrounds the center and includes a medicament and comprising at least 50% by weight of the chewing gum. The coating includes a macrosweetener.
Moreover, in an embodiment of the present invention, a method of manufacturing a medicament containing product is provided. The method comprising the steps of: preparing a gum center having water-soluble portion and a water-insoluble; coating the center with a powder and a syrup to create a coated product, at least one of the powder or syrup portion including a medicament; and the coated product comprising at least 50% by weight syrup and powder coating. The powder and syrup are coated on the gum center in alternating steps until a sufficient coating has been built up. Preferably the coating is not covered with a shellac or other finishing layer but rather maintains a matte finish.
Accordingly, an advantage of the present invention is to provide new methods for delivering medicaments or agents to an individual.
Furthermore, an advantage of the present invention is to provide an improved product containing a medicament.
Still further, an advantage of the present invention is to provide a method of delivering medicaments to an individual that provides for increase absorption and bioavailability as compared to medicaments that are designed to be absorbed in the GI tract.
Further, an advantage of the present invention is to provide a method of administering a medicament or agent to an individual at a lower level than is typically administered orally while still achieving the same effect.
Furthermore, an advantage of the present invention is to provide a method for administering medicaments or agents to an individual that heretofore were administered parentally.
Additionally, an advantage of the present invention is to provide a method for administering medicaments that is more palatable than current methods.
Another advantage of the present invention is to provide a method for enhancing the performance of an individual through the administration of an agent.
Moreover, an advantage of the present invention is to provide an improved method for drug delivery.
Still, an advantage of the present invention is to provide a method for creating a triggering effect that creates a synergistic effect with an agent that is present in the systemic circulation of the individual.
An advantage of the present invention is that a coated product is provided wherein the coating can absorb or lose moisture without apparent degradation.
Further, an advantage of the present invention is that a coated chewing gum product including medicament is provided having an extended shelf-life.